Genetic Biochemical Studies of Plant Steroid Signaling

描述(申请人提供)：激素和生长因子发出的信号是多细胞生物体生长调节的基本机制。类固醇是一种独特的激素，调节植物和动物的重要生理和发育过程。油菜素类固醇(BRs)是一种具有重要作用的植物类固醇激素，在结构和功能上与动物类固醇激素有相似之处，但通过不同的信号机制发挥作用。虽然动物类固醇激素通过核受体转录因子调节基因表达，或者通过膜结合受体激活非基因组反应，但BRs与细胞表面的受体激酶结合，通过信号转导级联机制调节核基因的表达。BR下游信号既涉及古老的信号蛋白，如GSK3类似蛋白和14-3-3蛋白，也涉及植物特有的DNA结合蛋白。我的实验室使用拟南芥作为模型系统，从生化、细胞生物学和生理水平上了解BR如何调控植物的生长和发育。我们研究了BRs如何通过控制关键转录因子BZR1的磷酸化状态和活性来调控基因的表达，并展示了BZR1如何调控BR反应基因的表达。我们计划利用遗传和生化方法继续研究BR信号转导途径，并计划研究BR信号转导途径如何与不同的发育过程以及调节共同发育过程的其他激素途径相联系。这项研究将促进我们对植物生长调控以及类固醇信号转导的理解。由于类固醇激素与人类包括癌症在内的许多重大疾病有关，这项研究将对农业和人类健康产生广泛的影响。

DESCRIPTION (provided by applicant): Signaling by hormones and growth factors is an essential mechanism of growth regulation in multicellular organisms. Steroids are unique hormones that regulate important physiological and developmental processes in both plants and animals. Brassinosteroids (BRs), the plant steroid hormone with essential roles, share structural and functional similarities with animal steroid hormones but act through a distinct signaling mechanism. While animal steroid hormones act either through nuclear receptor transcription factors to regulate gene expression or through membrane-bound receptors to activate non-genomic responses, BRs bind to a receptor kinase at the cell surface and regulate nuclear gene expression through a signal transduction cascade. Downstream BR signaling involves both ancient signaling proteins, such as GSK3-like kinases and 14-3-3 proteins, and plant specific DNA binding proteins. My laboratory uses Arabidopsis as the model system to understand how BR regulates plant growth and development at the biochemical, cell biological, and physiological levels. We have studied how BRs regulate gene expression by controlling the phosphorylation status and activity of the key transcription factor BZR1, and we have demonstrated how BZR1 regulates the expression of BR-responsive genes. We plan to continue our study of the BR signal transduction pathway using genetic and biochemical approaches, and we plan to study how the BR signal transduction pathway is connected to various developmental processes as well as to other hormonal pathways that regulate common developmental processes. This study will advance our understanding of plant growth regulation as well as steroid signaling in general. Because steroid hormones are involved in many major diseases including cancer in human, this study will have broad implications for both agriculture and human health.